The interaction between platelets and collagen marks the initiation of hemostasis. Adhesion of platelets to collagen is followed by platelet shape change, release, reversible aggregation and finally irreversible aggregation in the presence of fibrin. The mechanisms of each of these steps, as well as the specific components on the platelet surface and of the collagen moiety which are responsible for recognition and for the interaction remain unknown. Disorders in this interaction occur in a variety of diseases of the cardiovascular system (e.g. thrombosis, intravascular coagulation, atherosclerosis), of platelets (e.g. von Willebrand's disease, thrombastenia, Myeloproliferative disorders), and of collagen (e.g. Marfan's syndrome, rheumatoid arthritis) as well as in diseases such as cyrrhosis and in reactions of the circulatory system to dialysis, to external pumping, or to implants. We plan to perform in vitro studies of the interaction utilizing various physicochemical methods developed here over the past two years for quantitative evaluation of collagen multimerization, for sensitive detection of platelet aggregation, and for fluorometric measurements of the platelet system. These will be employed to (a) quantitate the adhesion reaction, (b) detect changes in the surface or in the chemistry of the platelets during adhesion, release and aggregation, (c) identify the mutual receptor sites on collagen and on platelets, (d) evaluate the effect of perturbants such as drugs, (e) compare differences between platelets and between collagens in normal and in diseased states. For all of the above we will utilized normal platelets in platelet rich plasma, after chromatographic washing, or as ghosts, and corresponding preparations from clinical platelet specimens. Comparable studies will also be made of soluble and insolubilized films of collagen from mammalian sources.